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1 August 2005

Volume 192, Number 3
The Journal of Infectious Diseases 2005;192:466–474
© 2005 by the Infectious Diseases Society of America. All rights reserved.
0022-1899/2005/19203-0014$15.00
DOI: 10.1086/431519
MAJOR ARTICLE

Molecular and Clinical Epidemiology of CXCR4‐Using HIV‐1 in a Large Population of Antiretroviral‐Naive Individuals

Zabrina L. Brumme,1,2

James Goodrich,3

Howard B. Mayer,3

Chanson J. Brumme,1

Bethany M. Henrick,1

Brian Wynhoven,1

Jerome J. Asselin,1

Peter K. Cheung,1

Robert S. Hogg,1

Julio S. G. Montaner,1,2 and

P. Richard Harrigan1,2

1BC Centre for Excellence in HIV/AIDS, St. Paul’s Hospital, and 2Faculty of Medicine, University of British Columbia, Canada; 3Pfizer, Inc., New London, Connecticut

Objective.We wished to characterize the epidemiological and clinical correlates of CXCR4‐using human immunodeficiency virus type 1 (HIV‐1) (“X4 variants”) in a cross‐sectional analysis of a large population of antiretroviral‐naive individuals.

Methods.HIV‐1 coreceptor use was determined in the last pretherapy plasma sample for 1191 individuals initiating triple‐combination therapy in British Columbia, Canada. Baseline variables investigated included sociodemographic characteristics, plasma viral load (pVL), CD4 cell count, AIDS diagnosis, HIV‐1 V3 loop sequence, and human CCR5 Δ32 genotype.

Results.Individuals harboring X4 variants ( of 979 phenotyped samples; 18.2%) displayed a poorer baseline clinical profile than individuals harboring exclusively CCR5‐using HIV‐1 (“R5 variants”) (median pVL, 175,000 vs. 120,000 copies of HIV‐1 RNA/mL [ ]; median CD4 cell count, 110 vs. 290 cells/mm3 [ ]). Individuals heterozygous for the CCR5 Δ32 deletion ( of 967; 13.2%) were at 2.5 times higher risk of harboring X4 variants, compared with those without the deletion (multivariate ). The presence of basic amino acids at codon 11 and/or codon 25 of HIV‐1 V3 ( of 955; 11.4%) was associated with a 9.1 times higher risk of harboring X4 variants (multivariate ), regardless of CCR5 Δ32 genotype. In multivariate analyses adjusting for baseline parameters, HIV‐1 coreceptor use was not found to be a significant predictor of survival or treatment response.

Conclusion.Baseline CD4 cell count, pVL, HIV‐1 V3 sequence, and CCR5 Δ32 genotype were the strongest determinants of CXCR4‐using HIV‐1 in this population. After adjustment for baseline parameters, the presence of X4 variants before initiation of highly active antiretroviral therapy was not independently associated with a poorer outcome of therapy.

Received 24 November 2004; accepted 3 March 2005; electronically published 23 June 2005.

Reprints or correspondence: Dr. P. Richard Harrigan, BC Centre for Excellence in HIV/AIDS, 603‐1081 Burrard St., Vancouver, BC, Canada V6Z 1Y6 ().

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  • Presented in part: 12th Conference on Retroviruses and Opportunistic Infections, Boston, 22–25 February 2005 (abstract 361).

    Financial support: Canadian Institutes for Health Research (Rx&D research grant; doctoral research award to Z.L.B.); Pfizer, Inc.; Michael Smith Foundation for Health Research (doctoral research award to Z.L.B.; Senior Scholar Award to R.S.H.).

    Potential conflicts of interest: J.G. and H.B.M. are employed by Pfizer, Inc.

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